PEG-400 Mediated an Efficient Green Synthesis of Isoxazolyl Indole-3-Carboxylic Acid Esters via Nentizescu Condensation Reaction and Their Anti-Inflammatory and Analgesic Activity

摘要

Polyethylene glycol-400 (PEG-400) has been discovered as an efficient and eco-friendly reaction medium for the synthesis of new isoxazolyl indole-3-carboxylic acid esters 11 from 4-amino- 3-methyl-5-styrylisoxazoles 7. Compounds 7 on treatment with b-keto ester 8 afforded the corresponding isoxazolylamino-2- butenoates 9 at ambient temperature in PEG-400. The Nentizescu condensation of compounds 9 with 1,4-benzoqui- none 10 to give the title compounds isoxazolyl indole-3- craboxylic acid esters 11 under PEG-400. Structures of com- pounds 9 and 11 were established on the basis of IR, 1~ HNMR, (13)~ CNMR and HRMS analysis. All the final compounds 11a–s were evaluated for their anti-inflammatory and analgesic activities. Among the compounds tested, the compounds 11 b, 11 g, 11 n, 11 o, 11 p and 11 s exhibited significant anti- inflammatory and potent analgesic activities as that of standard drugs. The advantages of this protocol are: operational simplicity, environmental safety, broad substrate scope, excel- lent functional group tolerance, and good yields. The PEG-400 can be recovered and reused.